Central autonomic network and Takotsubo cardiomyopathy: how left insular cortex interact?

This commentary refers to ‘Altered limbic and autonomic processing supports brain-heart axis in Takotsubo syndrome’, by C. Templin et al., pages 1183–1187. We read the interesting manuscript by Templin et al.,1 who reported that Takotsubo syndrome (TTS) patients had reduced resting state functional connectivity in parasympathetic- and sympathetic-associated subnetworks including the amygdala, hippocampus, and insular cortex (Ic) compared with controls. Specifically, TTS-related hypoconnected subnetwork was shown to be composed of the left anterior Ic, left posterior cingulate cortex, and bilateral medial orbitofrontal cortex. Recent studies have supported the notion that the cardiovascular system is regulated by a central autonomic network (CAN) consisting of Ic, anterior cingulate cortex, and amygdala.2 Because Ic is located in the region of the middle cerebral arteries, its structure tends to be exposed to a higher risk of cerebrovascular disease.2 And Ic damage has been associated with myocardial injury, increased brain natriuretic peptide, and TTS.2 Although several cerebral regions in relation to TTS were indicated in the manuscript by Templin et al.,1 the relationship between the left Ic hypoconnection and TTS pathophysiology was little discussed. In an earlier study,3 the right hemispheric inactivation induced an increase of high frequency of heart rate (HR) and blood pressure (BP), and the left inactivation induced an increase low frequency of HR and BP in patients with drug-refractory epilepsy. In addition, Oppenheimer et al.4 identified a site of cardiac representation within the Ic. While tachycardia or pressor effect was observed in the stimulation of the right Ic, bradycardia or depressor effect was significantly more common after stimulation of the left Ic.4 In the elderly hypertensives, the right Ic volume was significantly correlated with serum noradrenaline level, while the left Ic volume was significantly correlated with serum brain natriuretic peptide level.2 Moreover, we recently experienced the case diagnosed as herpes encephalitis with right Ic lesion had diffuse left ventricular (LV) hypokinesis at 1 week after admission.5 Cardiac 123I-meta-iodobenzylguanidine uptake scintigraphy revealed regional reduced uptake. Thus, LV hypokinesis was suggested to be derived from reduced sympathetic nervous system activity due to right Ic lesion.5 These results suggest that right hemisphere including the right Ic is predominantly associated with sympathetic autonomic tone, whereas left hemisphere including the left Ic is associated with parasympathetic autonomic tone. Because one possible pathophysiology of TTS has been shown to be sympathetic autonomic nervous system over activity,2 it is difficult to interpret that the left Ic was one of the nodes involved in the TTS-related sympathetic-associated hypoconnected subnetwork.1 Until now, there have been few reports assessing the functional connectivity of CAN in relation to TTS pathophysiology according to hemispheric laterality of Ic. The data presented in the manuscript by Templin et al.1 would make much more importance if the exact mechanism underlying that relationship were provided. Conflict of interest: none declared.